Alterations of monoallelic DNA methylation in breast cancer

Aim: to evaluate changes in the methylation status of cytosine residues in CpG islands, monoallelically methylated in the norm, in samples of malignant breast tumors. Methods. To determine CpG dinucleotides monoallelically methylated in tumor and normal breast tissues, we used the results of Xmal-RRBS genome-wide bisulfite sequencing obtained earlier. Changes in monoallelic methylation in tumors were visualized using histograms for different breast methylotypes. Results. In the genomes of moderately methylated tumors, normally methylated CpG dinucleotides have a tendency to an almost equiprobable methylation change to both the unmethylated and fully methylated states. In the genomes of hypermethylated tumors, normally monoallelically methylated CpG dinucleotides more often change their state to fully methylated. Conclusions. The observed nature of the changes suggests that the dynamics is dictated in moderately methylated tumors by processes that do not determine their vector, and in hypermethylated tumors, additionally, by a directed process that increases the methylation level of CpG dinucleotides. By analogy with the previously published results of a study of the dynamics of changes in methylation of imprinted loci in human tumors, we assume that the process of random determination of the vector of methylation changes is mediated by copy number aberrations at the regions of monoallelic DNA methylation. The reason for the equally probable bidirectional changes in monoallelic methylation may be a genomic imbalance that can randomly lead to deletions (or acquired uniparental disomy) of either the methylated or unmethylated allele.

Breast cancer, genome wide analysis of DNA methylation, monoallelic DNA methylation

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